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Blood Clotting

Outline

A. Five Stages in Hemostasis
    1. Vessel Spasm

    2. Formation of Platelet Plug

    3.Blood coagulation (Fibrin clot)

        a. extrinsic pathway (occurs in tissues0

        b. intrinsic pathway (occurs in vascular system when blood
            contacts injured vessel wall or sometimes activated by
            antigen-antibody reaction, drugs or circulatory debris)

        c. final conversion is fibrinogen to fibrin

    4. Clot Retraction
        a. fibrin stabilizing factor

    5. Clot Dissolution (Fibrinolysis)

        a. final step is conversion of plasminogen to plasmin

B. Disorders of Hemostasis
    1. Hypercoagulability states
        a. conditions that create hyper reactivity of platelet function
            1. atherosclerosis

            2. diabetes

            3. smoking

        b. conditions that increase clotting activity
            1. anything that increases venous stasis or alters balance
                between procoagulation and anticoagulation factors, e.g.
                pregnancy
                oral contraceptives
                immobility
                 malignancies

    2. Disseminated Intravascular Coagulation (DIC)
        a. clotting becomes altered, due to
            massive trauma
            burns
            sepsis
            shock
            infection
            malignancies
            blood transfusion reactions
            obstetrical conditions

        b.clotting becomes activated in widespread areas of
   circulation- microemboli form which plug up small
   peripheral vessels causing
     1. procoagulant factors to be used up- leading to bleeding
                throughout rest of body

     2. tissue to be deprived of oxygen - exacerbates shock

    3.Bleeding Disorders
        1. Impairment of Platelet Function
            a.malignancies
            b. radiation and drugs
            c. splenomegaly
            d. autoimmune response
    e. idiopathic
    f. aspirin (impairs adherence and aggregation of platelets)

2. Coagulation Defects
    a. Impaired synthesis (for example, liver disease can
        impair VIT K activation)

    b. Hereditary Defects
         1. Classic hemophilia (deficiency of Factor VIII) =
              80% of all hemophilia's

        2. Hemophilia B (Christmas Disease) (deficiency of
            Factor IX, 15% of cases

        3. Hemophilia C (deficiency of Factor XI), 55 of cases  

Discussion  

    Procoagulation and anticoagulation factors are always circulating in the inactive state in the blood, ready to either form a clot, should bleeding occur, and dissolve a clot when it's job is done. The liver synthesizes most of these factors, so liver disease can be a major cause of bleeding disorders. Just as it is important for the body to form a clot when needed, it is just as important to be able to dissolve that clot after the blood vessel has healed. Clots, although necessary at times, are always dangerous since pieces of them can break off at any time and lodge in a smaller vessel, occluding circulation to the tissue supplied by that vessel. Sometimes this can have disastrous consequences, as for instance, in the case of pulmonary embolism, or as a cause in CVA or MI.
In hemophilia the intrinsic coagulation pathway is impaired because of a genetic defect. The extrinsic pathway is unaffected. Hence a clot can be formed, eventually. But, the impairment of the intrinsic pathway causes excessive bleeding. The bleeding can occur anyplace in the body, but mostly it occurs into the joints, producing severe pain and, over a period of time, joint deformities.

    Clinically  

    Any situations that can lead to the inappropriate formation of clots is dangerous (by inappropriate is meant formation of a clot in the absence of a need for it to repair a damaged blood vessel). Venous stasis (as would occur with immobility, or can occur in other cases such as blood pooling in the atria due to Atrial fibrillation), hypercoagulabity and injury to the vessel wall are three factors that have long been recognized as leading to formation of clots. These three factors are referred to as Virchow's Triad. One should watch for them in clinical situations.
    There is a difference between anticoagulant drugs and fibrinolytic drugs. Anticoagulants prevent the formation of clots, whereas fibrinolytic agents dissolve a clot after it has already formed. Heparin and coumadin are both anticoagulants which are used in a wide variety of clinical situations. Heparin (produced normally by the body) interferes with prothrombin activator in the intrinsic pathway, inhibits action of thrombin on fibrinogen and inactivates thrombin. Heparin works immediately and its effect lasts 3-4 hours.It can only be given parenterally. The Activated Partial Thromboplastin Time (aPTT) (measures activity of intrinsic pathway) is useful for evaluating the response to anticoagulant therapy with heparin. Coumadin, which is taken P.O. decreases prothrombin and other procoagulation factors that require Vit. K. It acts at the level of the liver.. Prothrombin time (PT) (measures activity of extrinsic pathway) is useful in making decisions regarding coumadin usage. The values for PT have been standardized into a system of reporting based on an international normalized ratio (INR)
    Certain bacteria produce a fibrinolytic agent, streptokinase.Isolated and processed from bacteria, streptokinase is available as a drug for treatment in those situations where it is desirable to break up clots that have already formed, for example in deep vein thrombosis (DVT) or during the evolution of a myocardial infarction . Through recombinant gene technology, tissue plasmin activator (tPA) can now be produced in sufficient quantity to be administered as a medication.